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Cerebral Cortex, Vol. 13, No. 2, 144-154, February 2003
© 2003 Oxford University Press

Practice and Difficulty Evoke Anatomically and Pharmacologically Dissociable Brain Activation Dynamics

Ed Bullmore1,2, John Suckling1, Fernando Zelaya2, Chris Long2,3, Garry Honey1, Laurence Reed2, Carol Routledge4, Virginia Ng2, Paul Fletcher1, John Brown4 and Steve C.R. Williams2

1 University of Cambridge, Department of Psychiatry, Addenbrooke’s Hospital, Cambridge CB2 2QQ, , 2 Institute of Psychiatry, King’s College London, De Crespigny Park, London SE5 8AF, UK, , 3 Neuroscience Statistics Research Lab, Massachusetts General Hospital, Boston, MA, USA and , 4 GlaxoSmithKline, Clinical Research Unit, ACCI, Cambridge CB2 2GG, UK

Address correspondence to Professor E.T. Bullmore, Brain Mapping Unit, Department of Psychiatry, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK. Email: etb23{at}cam.ac.uk.

Brain activation is adaptive to task difficulty and practice. We used functional MRI to map brain systems activated by an object-location learning task in 24 healthy elderly volunteers each scanned following placebo and two of four active drugs studied. We distinguished a fronto-striatal system adaptive to difficulty from a posterior system adaptive to practice. Fronto-striatal response to increased cognitive load was significantly attenuated by scopolamine, sulpiride and methylphenidate; practice effects were not modulated by these drugs but were enhanced by diazepam. We also found enhancement by methylphenidate, and attenuation by sulpiride, of load response in premotor, cingulate and parietal regions comprising a spatial attention network. Difficulty and practice evoke anatomically and pharmacologically dissociable brain activation dynamics, which are probably mediated by different neurotransmitter systems in humans.


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